Get started
Work

Design, Synthesis, and Biological Evaluation of Novel Urea-Containing Carnosic Acid Derivatives with Anticancer Activity

Year: 2024
Type: article
Abstract: A series of novel carnosic acid 1 derivatives incorporating urea moieties at the C-20 position was synthesized and evaluated for their antiproliferative activity against the HCT116 colorectal cancer cell line. Most derivatives demonstrated enhanced antiproliferative activity compared to that of carnosic acid 1. The most promising derivatives were tested in other colorectal cancer cell lines (SW480, SW620, and Caco-2), melanoma (A375), and pancreatic cancer (MiaPaca-2). Derivative 14 consistently demonstrated the highest activity across all tested cancer cell lines, showing selectivity for cancer cells over normal cells. Further investigation of the mechanism of action in SW480 cells revealed that compound 14 induced cell cycle arrest at the G0/G1 phase by downregulating CDK4 and CDK6. Molecular docking studies revealed that compound 14 established several interactions with key residues in the active site of CDK6. Additionally, compound 14 also reduced ROS production. In summary, our results strongly indicate that compound 14 has potential as a lead compound in the development of innovative anticancer drugs.
DOI: 10.3390/ijms252413332
Authors: Sara P. S. P. Moura, Silvia Marín, Ismael Rufino, Rita C. Guedes, Marta Cascante, Jorge A. R. Salvador
Institutions: Centro de Neurociências e Biologia Celular, University of Coimbra, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Universitat de Barcelona, University of Lisbon
Language: English
Open Access status: gold
Estimated APC paid: $3,296
Funders: Generalitat de Catalunya, Institució Catalana de Recerca i Estudis Avançats, Universidade de Coimbra, Universidade de Lisboa, Fundação para a Ciência e a Tecnologia, Agència de Gestió d'Ajuts Universitaris i de Recerca, Instituto de Salud Carlos III, European Regional Development Fund
Awards: Novel abietane-type diterpenoid derivatives with potent anticancer activity, G1167214205, G1187920887, G1267941812, G1509308464, G1541464577, G1577006909, G1578237752, G1607784275, G1679090421, G1747174229, G184859499, G1893951279, G1919449872, Centro de Inovação em Biomedicina e Biotecnologia, G2007306547, G2037607178, G2051880127, G2198875670, G2287133727, G2326379152, G2370531804, G2532718879, G2595968322, G2632959804, G2644279276, G2705314997, G2713162615, G3175896773, G3258439967, G3267337789, G3295750263, G3335316771, G3361765969, G3398623617, G3400423363, G3757038852, G3908905116, G3920550538, G4011854498, G4015828041, G4129162949, G4173055396, G425256743, G4252945559, G4481743947, G4544514986, G4646977886, G4705738886, G4810541173, G4812071454, G4910381745, G5185804457, G5856876436, G6242129896, G6313478005, Centro de Inovação em Biomedicina e Biotecnologia, Instituto de Investigação do Medicamento, G6336487864, G6387409325, Do espaço químico à função biológica: uma viagem pela mão da UC-NMR, G6511684190, G6784240545, G6907760431, G6964224787, G6997658380, G7012136202, G7042061776, G7093375666, Centro de Inovação em Biomedicina e Biotecnologia - Laboratório Associado, G7408972871, G754618769, G7552834848, G7561159203, G7697053519, G7814811240, G7978180213, G8001130339, G809477656, G810402943, FFUL Computing Innovation Centre - Learn-Teach-Innovate-Transfer, Centro de Química - Coimbra, G8211996980, G8213223113, G8330672496, G8498264002, Instituto de Investigação do Medicamento, G8565970336, G955724782
OpenAlex ID: W4405329283
FWCI: 0.693
Cites: 111
Cited by: 6
Related to: 10